A comparative molecular docking study of crocetin with multiple receptors for the treatment of alzheimer's disease

Abstract

Background: Crocetin, an active constituent derived from Crocus sativus L. and Gardenia jasminoides, has shown to have multiple pharmacological activities such as memory booster, anti-oxidants, anti-inflammatory, and neuroprotective actions. Clinical trials on Saffron extract and a preclinical trial of Crocetin for neurodegenerative diseases directs probable use of Crocin in Alzheimer's disease (AD). The Crocin metabolizes into Crocetin after administration. The affinity of Crocetin to different receptor for AD on the basis of molecular docking has not yet been investigated. The present study was aimed to identify the affinity of Crocetin with different receptors involved in Alzheimer's pathogenesis by docking. Autodock Tools (MGL Tools), PYMOL, AutoDock Vina, Discovery studio 2021 client and SwissADME were used. Molecular docking simulation showed significant binding affinity of Crocetin to various receptors. It was found to bind significantly with different receptors like Vitamin D receptor (binding energy-7.9 kcal/mol), Receptor for advanced glycation end products (binding energy-7.5 kcal/mol) and NOD-like receptor pyrin domain-containing-3 (binding energy-7.4 kcal/mol). The results obtained suggest the usefulness of Crocetin in AD. Context: In this study, we have investigated the binding affinity of Crocetin on different receptors related to AD by performing molecular docking studies. Aim: Determination of binding affinity of Crocetin with different receptors involved in AD. Settings and Design: Auto dock vina, Pymol, Discovery studio, Auto dock Tools, Chemsketch, Swiss ADME. Methods: Molecular docking. Results: The Crocetin was found to have significant binding affinity to different receptors such as Vitamin D receptor (binding energy-7.9 kcal/mol), receptor for advanced glycation end products (binding energy-7.5 kcal/mol), and NOD-like receptor pyrin domain-containing-3 (binding energy-7.4 kcal/mol). Conclusions: The present study focuses on docking of Crocetin with different receptors related to the treatment of AD. The Crocetin was found to have a significant binding affinity with different receptors like Vitamin D receptor (binding energy-7.9 kcal/mol), Receptor for advanced glycation end products (binding energy-7.5 kcal/mol), and NOD-like receptor pyrin domain-containing-3 (binding energy-7.9 kcal/mol) while it exhibits moderate binding with receptor-like peroxisome proliferator-activated ϒ receptor (binding energy-7.1 kcal/mol), cannabinoid receptors (binding energy-7.1 kcal/mol) and ryanodine receptor (binding energy-7.0 kcal/mol). It showed the best potential to be developed into an anti-Alzheimer's drug due to its binding with multiple targets. From drug likeliness properties it can be seen that Crocetin can be absorbed by the human body and does not violate the Lipinski rule. Limitations of Study: Theoretical predictions are just consultative and have to be carefully verified by in vivo experiments.